title: Joint probability of statistical success of multiple phase III trials.
abstract: In drug development, after completion of phase II proof-of-concept trials, the sponsor needs to make a go/no-go decision to start expensive phase III trials. The probability of statistical success (PoSS) of the phase III trials based on data from earlier studies is an important factor in that decision-making process. Instead of statistical power, the predictive power of a phase III trial, which takes into account the uncertainty in the estimation of treatment effect from earlier studies, has been proposed to evaluate the PoSS of a single trial. However, regulatory authorities generally require statistical significance in two (or more) trials for marketing licensure. We show that the predictive statistics of two future trials are statistically correlated through use of the common observed data from earlier studies. Thus, the joint predictive power should not be evaluated as a simplistic product of the predictive powers of the individual trials. We develop the relevant formulae for the appropriate evaluation of the joint predictive power and provide numerical examples. Our methodology is further extended to the more complex phase III development scenario comprising more than two (K > 2) trials, that is, the evaluation of the PoSS of at least k₀ (k₀≤ K) trials from a program of K total trials.
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Zhang
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Zhang
mesh_terms: D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003657:Decision Making; D015195:Drug Design; D006801:Humans; D011336:Probability; D012107:Research Design; D035501:Uncertainty
keywords: joint predictive power; phase III trials; probability of statistical success